Inauen W, Emde C, Weber B, Armstrong D, Bettschen H U, Huber T, Scheurer U, Blum A L, Halter F, Merki H S
Gastrointestinal Unit, University Hospital, Inselspital Bern, Switzerland.
Gut. 1993 Aug;34(8):1025-31. doi: 10.1136/gut.34.8.1025.
The effect of ranitidine and cisapride on acid reflux and oesophageal motility was investigated in 18 patients with endoscopically verified erosive reflux oesophagitis. Each patient was treated with placebo, ranitidine (150 mg twice daily), and ranitidine (150 mg twice daily) plus cisapride (20 mg twice daily) in a double blind, double dummy, within subject, three way cross over design. Oesophageal acidity and motility were monitored under ambulatory conditions for 24 hours on the fourth day of treatment, after a wash out period of 10 days during which patients received only antacids for relief of symptoms. Acid reflux was monitored by a pH electrode located 5 cm above the lower oesophageal sphincter. Intraoesophageal pressure was simultaneously recorded from four transducers placed 20, 15, 10, and 5 cm above the lower oesophageal sphincter. Upright reflux was three times higher than supine reflux (median (range) 13.3 (3.7-35.0)% v 3.7 (0-37.6)% of the time with pH < 4.0, p < 0.01, n = 18). Compared with placebo, ranitidine decreased total reflux (from 10.0 (3.2-32.6)% to 6.4 (1.2-22.9)%, p < 0.01), upright reflux (p < 0.05), supine reflux (p < 0.001), and postprandial reflux (p < 0.01), but did not affect oesophageal motility. The combination of ranitidine with cisapride further diminished the acid reflux found with ranitidine--that is, cisapride led to an additional reduction of total reflux (from 6.4 (1.2-22.9)% to 3.7 (1.0-12.7)%, p < 0.01), supine reflux (p < 0.05), and postprandial reflux (p < 0.05). Cisapride also reduced both the number (p<0.01) and duration (p<0.05) of reflux episodes and significantly increased amplitude, duration, and propagation velocity of oesophageal contractions (p<0.05) but did not affect the number of contractions. The findings show that the 30% reduction of oesophageal acid exposure achieved by a conventional dose of ranitidine (150 mg twice daily) can be improved to more than 60% by combination with cisapride (20 mg twice daily). The cisapride induced increase in oesophageal contractile force and propagation velocity seems to enhance the clearance of gastro-oesophageal reflux. Combination of a histamine H2 receptor antagonist with a prokinetic agent may therefore provide an alternative treatment for reflux oesophagitis.
在18例经内镜证实为糜烂性反流性食管炎的患者中，研究了雷尼替丁和西沙必利对胃酸反流及食管动力的影响。采用双盲、双模拟、自身对照、三交叉试验设计，每位患者分别接受安慰剂、雷尼替丁（150毫克，每日两次）以及雷尼替丁（150毫克，每日两次）加西沙必利（20毫克，每日两次）治疗。在经过10天的洗脱期（期间患者仅服用抗酸剂缓解症状）后，于治疗的第四天在动态条件下监测食管酸度和动力24小时。通过位于食管下括约肌上方5厘米处的pH电极监测胃酸反流。同时从置于食管下括约肌上方20、15、10和5厘米处的四个传感器记录食管内压力。直立位反流比仰卧位反流高3倍（pH<4.0时的时间中位数（范围）分别为13.3（3.7 - 35.0）%和3.7（0 - 37.6）%，p<0.01，n = 18）。与安慰剂相比，雷尼替丁可降低总反流（从10.0（3.2 - 32.6）%降至6.4（1.2 - 22.9）%，p<0.01）、直立位反流（p<0.05）、仰卧位反流（p<0.001）以及餐后反流（p<0.01），但不影响食管动力。雷尼替丁与西沙必利联合使用可进一步减少雷尼替丁治疗时出现的胃酸反流——即西沙必利可使总反流进一步降低（从6.4（1.2 - 22.9）%降至3.7（1.0 - 12.7）%，p<0.01）、仰卧位反流（p<0.05）以及餐后反流（p<0.05）。西沙必利还可减少反流发作的次数（p<0.01）和持续时间（p<0.05），并显著增加食管收缩的幅度、持续时间和传播速度（p<0.05），但不影响收缩次数。研究结果表明，常规剂量的雷尼替丁（150毫克，每日两次）可使食管酸暴露降低30%，与西沙必利（20毫克，每日两次）联合使用时可将其提高至60%以上。西沙必利引起的食管收缩力和传播速度增加似乎可增强胃食管反流的清除。因此，组胺H2受体拮抗剂与促动力剂联合使用可能为反流性食管炎提供一种替代治疗方法。
